Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of Vitamin D and other UVB-Induced molecules

Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome

Objective To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT). Methods sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes. Results Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7–161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2–212.2) than in HC (10.7 pg/ml [IQR] 4.9–21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT −10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall. Conclusions Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS

Panspermia, Past and Present: Astrophysical and Biophysical Conditions for the Dissemination of Life in Space

Astronomically, there are viable mechanisms for distributing organic material throughout the Milky Way. Biologically, the destructive effects of ultraviolet light and cosmic rays means that the majority of organisms arrive broken and dead on a new world. The likelihood of conventional forms of panspermia must therefore be considered low. However, the information content of dam-aged biological molecules might serve to seed new life (necropanspermia).Comment: Accepted for publication in Space Science Review

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

Markets and marketing research on poverty and its alleviation: Summarizing an evolving logic toward human capabilities, well-being goals and transformation

Marketing practitioners and business scholars now view some of the world’s poorest communities as profitable growth markets. Hence a market-based approach to poverty alleviation has gathered momentum. This article traces the evolution of such a market-based approach over four decades and highlights a gradual trend away from a deficit-reduction approach (focused on constraints and justice) towards an opportunity-expansion approach (focused on capabilities and well-being). This trend is summarized in an analytical framework of human capabilities, well-being goals and transformative impact evolved from the literature. The framework is then used to analyse the practice of sanitation marketing, which has emerged as a key method in one of the highest priority domains in international development discourse – sanitation. The article concludes with a discussion of how contemporary work can further take forward the key tenets of the framework and guide the development of ‘good markets’ for the poor

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

Hybrid bubble chamber studies of K+ p and K- p interactions at 75-GeV/c

We propose to expose the FNAL 30' liquid hydrogen bubble chamber to K{sup +} and K{sup -} beams both at 75 GeV/c. Each exposure consists of 100,000 equivalent K pictures. We plan to use the upstream tagging system currently in place and a downstream spectrometer with acceptance considerably increased over that of the current PHC system. This new downstream system will also be equipped with a lead glass photon detector with good spatial and energy resolution. We will study comparison of K{sup +} and K{sup -} results, as well as results from {pi}{sup +}, {pi}{sup -} , and {bar p} beams at this energy which are the subject of separate proposals

Corporate social responsibility: The good, the bad and the ugly

In this article I critically analyze contemporary discourses of corporate social responsibility and related discourses of sustainability and corporate citizenship. I argue that despite their emancipatory rhetoric, discourses of corporate citizenship, social responsibility and sustainability are defined by narrow business interests and serve to curtail interests of external stakeholders. I provide an alternate perspective, one that views discourses of corporate citizenship, corporate social responsibility, and sustainability as ideological movements that are intended to legitimize and consolidate the power of large corporations. I also problematize the popular notion of organizational 'stakeholders'. I argue that stakeholder theory of the firm represents a form of stakeholder colonialism that serves to regulate the behavior of stakeholders. I conclude by discussing implications for critical management studies